Molecular Mechanism of the DNA Sequence Selectivity of 5-Halo-2 '-Deoxyuridines as Potential Radiosensitizers

作者：Wang Chun Rong; Lu Qing Bin^*

来源：Journal of the American Chemical Society, 2010, 132(42): 14710-14713.

DOI：10.1021/ja102883a

The 5-halo-2'-deoxyuridines bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU) are well-known photosensitizers for inducing DNA/RNA-protein cross-linking and potential radiosensitizers for radiotherapy of cancer. The dependence of the photosensitivity of BrdU and IdU on the DNA sequence has been well-observed, but it is unknown whether there is a similar DNA sequence selectivity in their radiosensitivity. Here we show a new ultrafast electron transfer (UET) mechanism for the likely DNA sequence dependence of the radiosensitivity of BrdU and IdU. Our femtosecond time-resolved transient laser absorption spectroscopic measurements provide the first real-time observation of the UET reactions of BrdU/IdU with the anion states of adenine and guanine. It is shown that the UET between BrdU and dA(star-) (dA(-)) is more effective than that between BrdU and dG(star-). This is related to the recent observation that dG(star-) is highly destructive while dA(-) is long-lived. This mechanistic understanding may lead to the improvement of BrdU and IdU to achieve sufficient radiosensitizing efficacy and the development of more effective radiosensitizers for clinical uses.

• 出版日期2010-10-27